Melanoma

1. Melanoma
By
Dr. Ihab Samy
lecturer of Surgical Oncology
National Cancer Institute
Cairo University
2014
Ihab Samy 2014

2. MALIGNANT MELANOMA
• Malignant melanoma is a malignancy of
melanocytes that occurs in the skin, eyes,
ears, gastrointestinal tract, leptomeninges,
and oral and genital mucous membranes.
• One of the most dangerous tumors,
melanoma has the ability to metastasize to
any organ, including the brain and heart.
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3. EPIDEMIOLOGY
• The incidence of malignant melanoma is increasing rapidly
worldwide.
• The median age at diagnosis is 57 years, and the median
age at death is 67 years.
• Whites have a 10-fold greater risk of developing cutaneous
melanoma than blacks, Asians, or Hispanics.
• Whites and blacks have a similar risk of developing plantar
melanoma. Noncutaneous melanomas (e.g., mucosal) are
more common in non-white populations.
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4. CLINICAL RISK FACTORS
• Fair-skinned persons.
• Common and Atypical Nevi.
• Giant Congenital Nevi.
• Personal History of Melanoma.
• Strong family history of melanoma with 2 or
more first-degree relatives affected.
• Ultraviolet (UV) radiation exposure, to both UVA
and UVB.
• Increasing age
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5. A
B
C
D
E
Asymmetry
Border irregularity
Colour variation
Diameter over 6 mm
Evolving (enlarging,
changing)
The ABCDs of Melanoma
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6. Biopsy Technique
• A full-thickness biopsy is done to interpret the maximum
tumor thickness and the presence or absence of ulceration
accurately.
• Excisional biopsy with a narrow margin of normal-appearing
skin is preferred for small lesions and can be performed on
most small lesions.
• A thin shave biopsy of suspicious lesions should be avoided,
because it may compromise histologic interpretation and
proper measurement of thickness.
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7. Immunohistochemistry for melanoma
• The S100 protein is a calcium-binding protein.
• HMB45 is an antibody against the gp-100 protein, a
glycoprotein considered to be part of the premelanosome
complex.
• Anti–MART-1 and anti–Melan-A.
• Other markers used to identify tumors of melanocytic
origin include microphthalmia-associated transcription
factor, melanoma-associated antigen, and tyrosinase.
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8. Clark's Levels
• Level I: Intraepidermal (melanoma in situ).
• Level II: Partial involvement of the papillary dermis by
single cells or small nests.
• Level III: Expansile nodule filling the papillary dermis and
widening it, impinging upon the reticular dermis. A few
cells may infiltrate the superficial reticular dermis.
• Level IV: Extension of multiple cells across a broad front
into the reticular dermis.
• Level V: Extension into the subcutaneous fat.
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9. Breslow Thickness
• T1: 1.0 mm or less
• T2: 1.1 to 2.0 mm
• T3: 2.1 to 4.0 mm
• T4: more than 4.0 mm
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10. T classification (thickness)
• TX - Primary tumor cannot be assessed (shave biopsy,
regressed primary)
• Tis - Melanoma in situ
• T1 - ≤1.0 mm (a: without ulceration, b: with ulceration)
• T2 - 1.01-2.0 mm (a: without ulceration, b: with
ulceration)
• T3 - 2.01-4.0 mm (a: without ulceration, b: with
ulceration)
• T4 - > 4.0 mm (a: without ulceration, b: with
ulceration)
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11. N classification
• N1 - 1 lymph node; a: micrometastasis (clinically occult), b:
macrometastasis (clinically apparent)
• N2 - 2-3 lymph nodes; a: micrometastasis, b:
macrometastasis, c: in transit met(s), satellite(s), without
metastatic lymph nodes (N2a: 2-3 nodes positive for
micrometastasis; N2b: 2-3 nodes positive for
macrometastasis; N2c: In transit met(s) or satellite(s)
without metastatic nodes)
• N3 - 4 or more metastatic nodes or matted nodes or in-
transit metastases or satellite(s) with metastatic node(s)
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12. M classification
• M1a - Distant skin, subcutaneous, or nodal
metastases, normal lactate dehydrogenase
(LDH) level
• M1b - Lung metastases, normal LDH level
• M1c - All other visceral metastases or any
distant metastases with an elevated LDH level
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13. Pathologic Stage Tumor Node Metastasis
0 Tis N0 M0
IA T1a N0 M0
IB T1b N0 M0
T2a N0 M0
IIA T2b N0 M0
T3a N0 M0
IIB T3b N0 M0
T4a N0 M0
IIC T4b N0 M0
IIIA T1–4a N1a M0
T1–4a N2a M0
IIIB T1–4b N1a M0
T1–4b N2a M0
T1–4a N1b M0
T1–4a N2b M0
T1–4a/b N2c M0
IIIC T1–4b N1b M0
T1–4b N2b M0
Any T N3 M0
IV Any T Any N M1
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14. Types of Melanoma
• Superficial spreading melanoma (about 70%
of diagnosed cases).
• Nodular melanoma (about 15% of diagnosed
cases).
• Lentigo maligna melanoma (about 10% of
diagnosed cases).
• Acral lentiginous melanoma (about 5% of
diagnosed cases).
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15. Non-pigmented Subtypes
• While uncommon, melanoma occasionally does not have
brown or black pigmentation. An uncommon subtype
called amelanotic melanoma usually appears as a pink or
red nodule (lump). 5% of all NMs are amelanotic
melanomas.
• Another uncommon subtype, desmoplastic neutrotrophic
melanoma (DNM), usually looks like a non-pigmented scar.
When a scar or keloid appears on the skin and the skin has
not been injured, DNM is suspected. The lesion also can
appear as a cyst that may or may not be pigmented. DNM
tends to appear on sun-damaged skin in elderly patients,
occurring mostly on the head and neck.
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16. Amelanotic melanoma
• Amelanotic melanoma appears as a lesion that has little or no color
(non-pigmented) or may appear red, pink or scarlike-white.
• It has an asymmetrical shape, and an irregular faintly pigmented
border.
• Any of the types of melanoma may be amelanotic, but a particular
amelanotic variety is called desmoplastic melanoma (DM). DM is
most commonly found in acral lentiginous melanomas located
subungually.
• Their atypical appearance leads to delay in diagnosis, so worse
prognosis .
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17. Treatment
• The mainstay of treatment of melanoma is
surgical, with 2 specific goals:
1. Excision of the primary lesion with
appropriate margins.
2. Evaluation of the nodal basin for staging
and disease clearance.
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18. • In Situ Melanoma (Stage 0) :should be excised using a 0.5-cm margin from all
edges of either the lesion or the prior surgical site. With in situ disease (Stage 0),
excision is the sole treatment.
• Lesions <1.0 mm Breslow Tumor Thickness or a Clark level II or III: wide local
excision with a 1.0-cm margin is the sole treatment.
• Lesions <1.0 mm Breslow Tumor Thickness with Adverse Features or Clark level
thickness IV or V, have a low, but real risk for occult nodal metastasis (ie, Stage IB
and Stage IIA lesions). These tumors should be resected with wide local excision of
1.0 cm from all margins and sentinel lymph node (SLN) evaluation should be
considered.
• Lesions Between 1.01 mm and 2.0 mm Breslow Tumor Thickness: wide local
excision with margins of 1.0 to 2.0 cm from all tumor edges based on the ability to
achieve primary closure. Patients with these lesions without clinical evidence of
regional nodal disease should undergo sentinel lymph node evaluation.
• Lesions >2.01 mm Breslow Tumor Thickness: wide local excision with 2.0 cm radial
margins from all tumor or prior surgical excision margins. Patients with these
lesions without clinical evidence of regional nodal disease or metastatic disease
from staging studies should undergo sentinel lymph node evaluation.
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19. Management of Lymph Nodes
• The use of sentinel lymph node biopsy in
melanoma is accepted as an appropriate method
of accurately staging individuals who may have
occult nodal metastasis.
• With the current AJCC staging model, all
individuals with a Stage Ib or higher melanoma
without clinically positive lymph nodes should be
offered a sentinel lymph node biopsy.
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20. • Clinically palpable lymph nodes should be
considered to have regional disease. A complete
regional lymphadenectomy is indicated.
• A complete lymph node dissection should include
an anatomically complete dissection of the entire
nodal basin involved.
• In the axilla this is usually a Level I and II axillary
dissection.
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21. Adjuvant therapy
• Currently interferon-ɑ2B is the only adjuvant
therapy regimen for malignant melanoma
approved by the Food and Drug Administration.
• Numerous evaluations with different dose
regimens and timing have all concluded that
although there is an extension of relapse-free
state, overall survival to 12.6 years is equivalent.
• The use of such a regimen should be made on an
individual patient basis.
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22. Stage IV and metastatic melanoma
• If at the time of presentation it is established that the
patient can undergo primary resection of the initial lesion
in conjunction with the solitary distant disease, this should
be attempted.
• Following surgery the patient should be offered adjuvant
therapy with interferon-ɑ2B or a clinical trial.
• Those patients who are not candidates for resection due to
either widespread metastatic disease or incomplete
resection should be treated with an advanced
chemotherapy regimen or referred for clinical trials.
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23. Isolated limb perfusion
• The arterial supply and venous drainage are
surgically isolated through an open incision, and
an oxygenated extracorporeal circuit is used to
circulate chemotherapeutic agents for 1 to 1.5
hours.
• Melphalan is typically used as a
chemotherapeutic agent, and the limb
temperature is typically elevated to 39 to 40°C
with a tourniquet in place.
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24. Isolated Limb Infusion
• Isolated limb perfusion can be effective for in-
transit metastases, however it is time- and
resource-consuming and can be toxic.
• One alternative to this approach involves
normothermic isolated limb infusion (ILI).
• Melphalan is typically used as a
chemotherapeutic agent.
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25. Isolated limb perfusion Isolated limb infusion
Technically complex
Open surgical exposure of vessels for
catheter insertion
4 to 6 hours duration
Complex and expensive equipment
Higher perfusion pressures predispose to
systemic leakage
Limb tissues oxygenated, with normal
blood gases maintained
Hyperthermia (>41°C can be achieved)
General anesthesia required
Technically simple
Percutaneous vascular catheter insertion
in radiology department
Approximately 1 hour
Equipment requirements modest
Low pressure system, effective vascular
isolation with tourniquet
Progressive hypoxia and acidosis
Usually not possible to raise limb
temperature above 40°C
Possible with regional anesthesia
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26. Case Presentation
• 65 years od female patient presenting with
large left iliac mass extending to left lumbar
and hypochondrial regions.
• History 2 months ago of excision of a small
exuberant heel ulcer about 1.5 X 1 cm.
• Pathology revealed: Amelanotic melanoma,
T4b, Clark’s level V; focally infiltrated surgical
margins.
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29. • CT Abdomen and pelvis (13-11-2011): Large
oblong retroperitoneal cystic collection at left
iliac region extending to left lumbar region
measuring 22 X 5 X4 cm. Extending sup. To
reach lower pole of spleen, displacing lt.
kidney medially + multiple enlarged inguino-
iliac LNs 1-3.5 cm. in diameter.
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32. • Follow- up CT Abdomen and pelvis (07-12-
2011): Progressive course since the last study
regarding the left ilio-lumbar cystic mass and
stationary course of lymphadenopathy.
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35. • CT guided aspiration cytology of 5 cc. of
turbid hemorrhagic fluid on (13-12-2011):
Exudative reaction.
(No Atypia or Malignancy)
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36. • Exploration done on 15-01-2012 through a
generous midline incision revealed a large
cystic mass covered by omentum occupying
the lt. iliac, lumbar and hypochondrial fossae.
• The mass was dissected from lt. ureter and
iliac vessels inferiorly up to lt. kidney, stomach
and spleen superiorly
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41. Left ureter after its complete dissection and release from the
mass.
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42. • Complete inguino-iliac lymphadenectomy was
done after excision of the mass in toto with
the overlying omentum.
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44. Complete iliac nodal dissection
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45. The residual heel ulcer was completely excised with safety
margin and left raw to heal by granulation tissue
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46. Specimens removed
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47. • No postoperative complications and the
patient was discharged on 24-01-2012.
• Follow-up showed no late complications and
good healing of the area excised at the heel.
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49. Pathology report
• Large metastatic mass 20 X 20 X 13 cm. of
malignant melanoma, congested omental
tissue.
• Totally collected 15 lymph nodes with 7
showed metastatic deposits.
• Skin of heel excised showed NO remnant of
tumor tissue.
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50. The patient now is receiving Interferon and
chemotherapy and she is free till now from local
recurrence and distant metastases.
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51. Thank you
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